VDAC1

GeneName

VDAC1

Summary

VDAC1, also known as VDAC, VDAC-1, or hVDAC1, is a 31kDa protein located primarily in the mitochondrial outer membrane, where it forms channels that facilitate the transport of ions and metabolites across the membrane. It plays a crucial role in mitochondrial function by regulating the flow of anions and metabolites, thus influencing processes such as apoptosis, calcium homeostasis, and energy metabolism. VDAC1 is also involved in interactions with various proteins, including those linked to lipid transport and cellular signalling, and is found in cellular structures such as the plasma membrane and synapses.

Importance

VDAC1 is relevant to: - Mitochondrial function and energy metabolism due to its role in ion and metabolite transport - Apoptosis regulation, impacting cancer research and therapeutic strategies - Neurodegenerative diseases through its involvement in neuronal signalling and synaptic transmission - Cellular stress responses, particularly in the context of reactive oxygen species and autophagy regulation

Top Products

For researchers investigating VDAC1, we recommend two excellent primary antibodies that cater to different experimental needs. The first is the well-cited polyclonal antibody, Anti-VDAC1/Porin antibody - Mitochondrial Loading Control (ab34726), which has garnered 70 citations, highlighting its reliability in immunohistochemistry (IHC). This antibody is a trusted choice for those focusing on mitochondrial studies.Additionally, we offer the recombinant antibody, Anti-VDAC1/Porin antibody [EPR27552-6] (ab306581), which has been validated in knockout models and is suitable for both Western blotting (WB) and IHC. With 5 citations, this product provides the batch-to-batch consistency that researchers often seek in their experiments. Together, these antibodies provide a robust toolkit for studying VDAC1 effectively.

Abcam Product Citation Summary

The data indicates a significant focus on VDAC1 in various studies related to mitochondrial function, dynamics, and pathology across multiple species, particularly in mouse and human models. The use of the Abcam antibody ab14734 in Western blotting highlights its role in investigating mitochondrial processes, including responses to stress, cellular dynamics, and disease mechanisms such as ischemia-reperfusion injury and cancer. The studies encompass a wide range of biological contexts, suggesting VDAC1's importance in cellular metabolism and health.

Abcam Product Citation Table

Domain

Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands (PubMed:18755977, PubMed:18832158). The helical N-terminus folds back into the pore opening and plays a role in voltage-gated channel activity (PubMed:18755977, PubMed:18832158).

Function

Non-selective voltage-gated ion channel that mediates the transport of anions and cations through the mitochondrion outer membrane and plasma membrane (PubMed:10661876, PubMed:11845315, PubMed:18755977, PubMed:30061676, PubMed:8420959). The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis (PubMed:10661876, PubMed:11845315, PubMed:18755977, PubMed:8420959). It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV (PubMed:10661876, PubMed:18755977, PubMed:8420959). The open state has a weak anion selectivity whereas the closed state is cation-selective (PubMed:18755977, PubMed:8420959). Binds various signaling molecules, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterols cholesterol and oxysterol (PubMed:18755977, PubMed:31015432). In depolarized mitochondria, acts downstream of PRKN and PINK1 to promote mitophagy or prevent apoptosis; polyubiquitination by PRKN promotes mitophagy, while monoubiquitination by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis (PubMed:15033708, PubMed:25296756). May mediate ATP export from cells (PubMed:30061676). Part of a complex composed of HSPA9, ITPR1 and VDAC1 that regulates mitochondrial calcium-dependent apoptosis by facilitating calcium transport from the ER lumen to the mitochondria intermembrane space thus providing calcium for the downstream calcium channel MCU that directly releases it into mitochondria matrix (By similarity). Mediates cytochrome c efflux (PubMed:20230784).

Catalyzes the scrambling of phospholipids across the outer mitochondrial membrane; the mechanism is unrelated to channel activity and is capable of translocating both anionic and zwitterionic phospholipids.

Post-translational modifications

Phosphorylation at Ser-193 by NEK1 promotes the closed conformational state preventing excessive mitochondrial membrane permeability and subsequent apoptotic cell death after injury (PubMed:20230784). Phosphorylation by the AKT-GSK3B axis stabilizes the protein probably by preventing ubiquitin-mediated proteasomal degradation.

Ubiquitinated (PubMed:25621951, PubMed:32047033). Undergoes monoubiquitination and polyubiquitination by PRKN; monoubiquitination at Lys-274 inhibits apoptosis, whereas polyubiquitination leads to its degradation and promotes mitophagy (PubMed:25621951, PubMed:32047033). Deubiquitinated by USP30 (PubMed:25621951).

Sequence Similarities

Belongs to the eukaryotic mitochondrial porin family.

Tissue Specificity

Expressed in erythrocytes (at protein level) (PubMed:27641616). Expressed in heart, liver and skeletal muscle (PubMed:8420959).

Cellular localization

• Mitochondrion outer membrane
• Multi-pass membrane protein
• Cell membrane
• Multi-pass membrane protein
• Membrane raft
• Multi-pass membrane protein
• Found in a complex with HSPA9 and VDAC1 at the endoplasmic reticulum-mitochondria contact sites.

Alternative names

VDAC, VDAC1, Non-selective voltage-gated ion channel VDAC1, Outer mitochondrial membrane protein porin 1, Plasmalemmal porin, Porin 31HL, Porin 31HM, Voltage-dependent anion-selective channel protein 1, VDAC-1, hVDAC1

Database links

swissprot:P21796 entrezGene:7416 omim:604492

Other research areas

• Immunology & Infectious Disease